Integrating influenza antigenic dynamics with molecular evolution

Abstract

Influenza viruses undergo continual antigenic evolution allowing mutant viruses to evade host immunity acquired to previous virus strains. Antigenic phenotype is often assessed through pairwise measurement of cross-reactivity between influenza strains using the hemagglutination inhibition (HI) assay. Here, we extend previous approaches to antigenic cartography, and simultaneously characterize antigenic and genetic evolution by modeling the diffusion of antigenic phenotype over a shared virus phylogeny. Using HI data from influenza lineages A/H3N2, A/H1N1, B/Victoria and B/Yamagata, we determine patterns of antigenic drift across viral lineages, showing that A/H3N2 evolves faster and in a more punctuated fashion than other influenza lineages. We also show that year-to-year antigenic drift appears to drive incidence patterns within each influenza lineage. This work makes possible substantial future advances in investigating the dynamics of influenza and other antigenically-variable pathogens by providing a model that intimately combines molecular and antigenic evolution.DOI: http://dx.doi.org/10.7554/eLife.01914.001

The beneficial effects of vaccination on the evolution of seasonal influenza

“…1A), characteristic of H3N2's antigenic evolution [37,38]. Antigenic evolution occurs at an average rate of 1.09 antigenic units per year (SD = 0.14), comparable to observed an observed rate of 1.01 antigenic units per year [38]. The mean annual incidence is 9.0% (SD = 1.0%).…”

“…1D). This space is analogous to the main components after multidimensional scaling of pairwise measurements of cross-reactivity in hemagglutination inhibition (HI) assays, where one antigenic unit of distance represents a twofold dilution of antiserum [37,38]. Each antigenic unit difference in distance between strains increases susceptibility by 7% (Fig.…”

“…Viral populations that are too diverse have the potential to cause high morbidity because hosts are unlikely to have immunity against many antigenic variants. Influenza subtypes H1N1 and B evolve antigenically slower than H3N2 but have greater genetic (and in the case of B, antigenic) diversity at any time [34,38,43,44] Thus, we chose to examine whether vaccination, by affecting antigenic evolution, could also impact diversification.…”

“…For computational efficiency, individuals cannot be coinfected. Antigenic phenotypes are represented as points in 2-dimensional Euclidean space, analogous to antigenic maps produced using pairwise measurements of serum cross-reactivity [37,38]. One antigenic unit corresponds to a two-fold dilution in antiserum in a hemagglutination inhibition (HI) assay.…”

“…First, because antigenic phenotypes evolve roughly linearly in two dimensions [36][37][38], we measured the cumulative amount of antigenic evolution by calculating the antigenic distance between the founding strain's antigenic phenotype and the average antigenic phenotype of strains circulating at the end of the simulation (Fig. 1).…”